Autoimmunity and oxidatively modified autoantigens
Autoimmunity and oxidatively modified autoantigens
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DOI：
10.1016/j.autrev.2008.04.019
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发表时间：
2008-07-01
影响因子：
13.6
通讯作者：
Scofield, R. Hal
中科院分区：
文献类型：
--
作者：
Kurien, Biji T.;Scofield, R. Hal
活性氧介导的氧化损伤导致有害副产品产生。这些分子修饰的氧化过程本身和蛋白质是细胞毒性和疾病发病机理的重要介质。醛产物，主要是4-羟基-2-烷烃，与蛋白质形成加合物，并使其具有高度免疫原性。以这种方式修饰的蛋白质已被证明可以在多种疾病中诱导病原抗体，包括全身性红斑狼疮（SLE），酒精性肝病，糖尿病（DM）和类风湿关节炎（RA）。 8-氧化氧化物（氧化修饰的DNA）和氧化的低密度脂蛋白（LDL）发生在SLE中，这种疾病是一种严重的问题。此外，用4-羟基-2-非纳尔（HNE）修饰的60 kd RO自动抗原的免疫接种会在SLE的动物模型中诱导加速的表位扩散。已显示晚期糖基化最终产物（年龄）戊糖苷和年龄改良的IgG与RA疾病活性相关。氧化修饰的谷氨酸脱羧酶在1型DM中很重要，而针对氧化LDL的自身抗体在Behcet氏病中普遍存在。硬皮病特异性自身抗原的碎片是由于氧化修饰而发生的，被认为是通过释放隐性表位来产生自身抗体的。抗氧化剂的给药是预防或改善自身免疫性疾病的可行未经尝试的替代方案，特别是由于氧化性损伤涉及自身免疫性的压倒性证据。但是，应根据心血管疾病中使用抗氧化剂而获得的令人失望的结果来查看这一点。由Elsevier B.V.出版
Oxidative damage mediated by reactive oxygen species results in the generation of deleterious by-products. The oxidation process itself and the proteins modified by these molecules are important mediators of cell toxicity and disease pathogenesis. Aldehydic products, mainly the 4-hydroxy-2-alkenals, form adducts with proteins and make them highly immunogenic. Proteins modified in this manner have been shown to induce pathogenic antibodies in a variety of diseases including systemic lupus erythematosus (SLE), alcoholic liver disease, diabetes mellitus (DM) and rheumatoid arthritis (RA). 8-oxodeoxyguanine (oxidatively modified DNA) and oxidized low-density lipoproteins (LDL) occur in SLE, a disease in which premature atherosclerosis is a serious problem. In addition, immunization with 4-hydroxy-2-nonenal (HNE) modified 60 kD Ro autoantigen induces an accelerated epitope spreading in an animal model of SLE. Advanced glycation end product (AGE) pentosidine and AGE modified IgG have been shown to correlate with RA disease activity. Oxidatively modified glutamic acid decarboxylase is important in type 1 DM, while autoantibodies against oxidized LDL are prevalent in Behcet's disease. The fragmentation of scleroderma specific autoantigens occurs as a result of oxidative modification and is thought to be responsible for the production of autoantibodies through the release of cryptic epitopes. The administration of antioxidants is a viable untried alternative for preventing or ameliorating autoimmune disease, particularly on account of the overwhelming evidence for the involvement of oxidative damage in autoimmunity. However, this should be viewed in the light of disappointing results obtained with the use of antioxidants in cardiovascular disease. Published by Elsevier B.V.